The present invention relates in general to hollow fiber membranes and specifically to polysulfone ultrafiltration hollow fiber membranes useful for hemodialysis.
The membrane art may be divided into microfiltration, ultrafiltration and dialysis. Each of these categories involves specific criteria and hence skills as evidenced by the following basic differentiation. Microfiltration may be defined as the separation of particles; ultrafiltration as the separation of molecules, primarily macromolecules; and dialysis as the separation of molecules in the ionic range. Thus it is a general objective of the present invention to overcome the specific problems encountered by the dialysis membrane art as enumerated below.
Dialysis primarily involves the migration of molecules across the membrane by diffusion processes governed by a concentration gradient. In hemodialysis, diffusion is passive and molecules are transferred from a region of high concentration to a region of lower concentration. The rate of movement of each molecular species is called its clearance. Clearance is directly proportional to the concentration gradient, diffusion constant of the molecule, temperature, thickness of the membrane and area of the membrane exposed to the fluid. In simple terms, the larger the concentration gradient, the smaller and more spherical the molecule, the higher the temperature, the thinner the membrane and the greater the membrane area exposed, the more rapidly the molecules move, i.e. the higher the clearance. Accordingly, it is a primary objective of the present invention to produce a high flux membrane taking into consideration the aforementioned criteria.
Hyrodynamic flow, the bulk movement of the fluid through a porous medium, is an additional factor to be considered in membrane filtration. In simple terms, the rate of flow of fluid through a porous membrane is directly proportional to the permeability or porosity of the medium, the pressure difference across the membrane, and inversely proportional to the viscosity of the fluid. Thus, the greater the porosity, the greater the pressure difference, and the less viscous the fluid the greater the flow. The present invention again successfully addresses these criteria in a novel and elegant manner.
A further prior art perceived problem to be overcome is fouling. Fouling is the buildup of material on the surface of the membrane which leads to clogging of the pores and hence decreased permeability.
Still a further obstacle to be overcome is concentration polarization, the concentration of a solute near the membrane surface. Increased solute concentration decreases flow rate.
In addition to the aforementioned problems, numerous additional problems are encountered in the kidney dialysis arena. The synthetic membrane art attempts to approximate the natural kidney ultrafiltration of the blood through the glomerular capillaries to remove waste products. The flow through the dialyzer units must be speedy to minimize concentration polarization but no so speedy as to cause denaturation of lysis of the blood components.
The prior art has attempted to solve the aforementioned inherent problems in various novel ways with varying degrees of success. Thus, for instance, flow rates have been increased by the arrival of anisotropic membranes, which have in contrast to earlier isotropic membranes, unequal pore openings on both sides or surfaces of the membrane. Rates were further increased by the advent of hollow fiber membranes which provide for a large filtration area per unit volume and efficient laminar flow to reduce concentration polarization effects.
To assure biocompatibility, most hemodialysis membranes are made of cellulose, however, synthetic membranes are available. Polysulfone membranes are highly biocompatible and have as such been employed in the filtration industry. However, primarily only in the microfiltration industry which as previously outlined deals with a much different set of problems than the ultrafiltration industry and more specifically the hemodialysis industry. While not to be construed to be a comprehensive survey of the art, the following patents are nevertheless considered illustrative of the polysulfone membrane art.
U.S. Pat. No. 4,906,375 issued to Fresenius discloses: "An asymmetric microporous wettable hollow fiber, consisting essentially of an inner barrier layer and an outer foam-like supporting structure said fiber comprising a hydrophobic first organic polymer in an amount equal to 90 to 99% by weight and 10 to 1% by weight of polyvinyl pyrrolidone which is produced by the following steps: PA0 U.S. Pat. No. 4,874,522 issued to Okamoto discloses: "A hollow fiber membrane comprising a polysulfone hollow fiber having on its inner surface a dense skin layer having no pores observable even with a scanning electron microscope (SEM) of magnification of 10,000 on its outer surface micropores having an average pore diameter of 500 to 5000 .ANG. at a fractional surface porosity of 5 to 50%, and a microporous structure inside said membrane, said membrane exhibiting properties which render it suitable for filtering body fluids and having permeabilities of serum albumin and inuline of not more than 10% and not less than 50% respectively, and a water permeability of not less than 60 ml/mm Hg.m.sup.2 Hr.
a) wet spinning a polymer solution made up of a solvent, of 12 to 20% by weight of the first said polymer and 2 to 10% by weight of the polyvinyl pyrrolidone, said solution having a viscosity of 500 to 3,000 cps, through a ring duct of a spinnerette having an external ring duct and an internal hollow core, PA1 b) simultaneously passing through said hollow internal core a precipitant solution comprising an aprotic solvent in conjunction with at least 25% by weight of a non solvent which acts in an outward direction on the polymer solution after issuing from the spinneret, PA1 c) casting into an aqueous washing bath, said spinerette and the upper surface of said washing bath being separated by an air gap, said air gap being to provided that full precipitation of components will have occurred before the precipitated polymer solution enters said washing bath thereby, PA1 d) dissolving out and washing away a substantial portion of the polyvinyl pyrrolidone and of the said solvent, to form a fiber having a high clearance rate according to DIN 58352, of 200-290 ml/min for urea and 200-250 ml/min for creatinine and phosphate, at a blood flow rate of 300 ml/min, for fibers having 1.25 m.sup.2 of active surface."
While this membrane has a high level of hydraulic permeability, and does not incur an oxygen decrease, it leaches polyvinyl pyrrolidine (PVP) which makes it less biocompatible. Morphologically speaking, the membrane has a uniform microporous barrier layer which has a pore diameter of 0.1 to 2 microns.
HEMOFLOW by Fresenius AG is a sponge-like membrane having micropores of about 6,000 .ANG. diameter on its outer surface and 500 .ANG. diameter pores on its inner surface.
Notably, the hollow fiber structure of this invention is a sponge-like structure having substantially no large cavities.
Given the aforementioned criteria and disadvantages of the prior art, the task of the present invention can be simply stated to provide a novel ultrafiltration hollow fiber membrane which more closely approximates actual kidney filtration by taking into consideration all the heretofore mentioned criteria and specifically providing for a mechanically strong biocompatible, i.e. no leaching; high flux, high solute clearance, decreased leukopenia, apoxia and cell lysis, and decreased pyrogen admittance.